{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:55:55Z","timestamp":1790675755376,"version":"4.1.0"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Cardiac rupture is a catastrophic complication of acute myocardial infarction (AMI), with poorly understood molecular mechanisms and no available therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Plasma samples were obtained from patients with AMI and animal models, while left ventricular tissue was collected from AMI mice. An unbiased proteomics analysis identified proteins significantly altered in patients with AMI with cardiac rupture. To explore causal relationships and underlying mechanisms, we used loss- and gain-of-function animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Proteomics analysis revealed that 9 proteins were significantly upregulated and 24 proteins were significantly downregulated in patients with AMI with cardiac rupture compared with those without. Among these, SMOC-1 (secreted modular calcium-binding protein 1) was the most significantly upregulated protein. Validation in extended patient cohorts and animal models confirmed these findings. A time-course study revealed that SMOC-1 expression was transiently elevated, peaking 1 day after AMI and returning to baseline within a week. Immunological and cell-specific analyses identified cardiomyocytes as the predominant source of SMOC-1 in response to AMI. Surprisingly, cardiomyocyte-specific SMOC-1 knockout doubled the incidence of post-AMI cardiac rupture and reduced survival, while adeno-associated virus serotype 9\u2013mediated SMOC-1 overexpression significantly decreased cardiac rupture rates. Mechanistic studies revealed that cardiomyocyte-derived SMOC-1 supports fibrosis by activating fibroblasts, enhancing collagen synthesis, and promoting collagen maturation, all of which are critical for the formation of reparative scars. SMOC-1 was shown to bind TGF-\u03b2R1 (transforming growth factor \u03b2 receptor 1) in fibroblasts, recruiting EPRS (glutamyl-prolyl-tRNA synthetase) to form a signaling complex that activates the Smad pathway. Inhibiting EPRS abolished the profibrotic effects of SMOC-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our study provides the first evidence that the transient upregulation and secretion of cardiomyocyte-derived SMOC-1 constitute an intrinsic profibrotic and antirupture response to severe ischemic injury. However, this natural protective mechanism is insufficient to fully prevent cardiac rupture, highlighting the potential of enhancing the SMOC-1 pathway as a promising therapeutic strategy to mitigate cardiac rupture and reduce AMI-associated mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.079324","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:01:55Z","timestamp":1790672515000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Secreted Modular Calcium-Binding Protein 1 as a Novel Endogenous Protective Molecule Against Acute Myocardial Infarction\u2013Induced Cardiac Rupture"],"prefix":"10.1161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4881-695X","authenticated-orcid":true,"given":"Wei","family":"Gong","sequence":"first","affiliation":[{"name":"Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (W.G., S.L., Z.Z., Y.Y., H.A., Y.L., S.N.)."},{"name":"National Clinical Research Center for Cardiovascular Diseases, Beijing, China (W.G., S.L., Z.Z., Y.Y., H.A., Y.L., S.N.)."},{"name":"Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China (W.G., S.L., Z.Z., Y.Y., H.A., Y.L., S.N.)."},{"name":"Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, China (W.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China (W.G., S.L., Z.Z., Y.Y., H.A., Y.L., S.N.)."},{"name":"National Clinical Research Center for Cardiovascular Diseases, Beijing, China (W.G., S.L., Z.Z., Y.Y., H.A., Y.L., 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